Abstract
Wilson disease (WD) is an autosomal recessive disorder of copper transport which maps to chromosome 13q14.3. In pursuit of the WD gene, we developed yeast artificial chromosome and cosmid contigs, and microsatellite markers which span the WD gene region. Linkage disequilibrium and haplotype analysis of 115 WD families confined the disease locus to a single marker interval. A candidate cDNA clone was mapped to this interval which, as shown in the accompanying paper, is very likely the WD gene. Our haplotype and mutation analyses predict that approximately half of all WD mutations will be rare in the American and Russian populations.
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References
Scheinberg, I.H. & Sternlieb, I., Problems in Internal Medicine. Volume XXIII (Smith, Jr, LH.) (Saunders, 1984).
Frydman, M. et al. Assignment of the gene for Wilson disease to chromosome 13: Linkage to the esterase D locus. Proc. natn. Acad. Sci. U.S.A. 82, 1819–1821 (1985).
Bonne-Tamir, B. et al. Evidence for linkage between Wilsons disease and esterase D in three kindreds: detection of linkage for an autosomal recessive disorder in the family study method. Genet Epidemiol. 3, 201–209 (1986).
Bowcock, A.M. et al. Eight closely linked loci place the Wilson disease locus within 13q14-q21. Am. J. hum. Genet. 43, 664–674 (1988).
Houwen, R.H.J. et al. Close linkage of the Wilsons disease locus to D13S12 in the chromosomal region 13q21 and not to EST in 13q14. Hum. Genet. 85, 560–562 (1990).
Farrer, L.A. et al. Predictive testing for Wilsons disease using tightly linked and flanking DNA markers. Neurology 41, 992–999 (1991).
Stewart, E.A. et al. Polymorphic microsatellites and Wilson Disease (WD). Am. J. hum. Genet. 53, 864–673 (1993).
Bowcock, A.M. et al. A contiguous linkage map of chromosome 13q with 39 distinct loci separated on avertage by 5.1 centimorgans. Genomics 11, 517–529 (1991).
Tanzi, R.E. et al. Identification of the Wilson disease gene; a copper transporting ATPase with homology to the Menkes disease gene. Nature Genet. 5, 344–350 (1993).
Fischer, S.G. et al. Assembly of ordered contigs from YAC-selected cosmids of human chromosome 13. (in the press).
Bellanne-Chantelot, C. et al. Mapping the whole human genome by fingerprinting Yeast Artificial chromosomes. Cell 70, 1059–1068 (1992).
Kleyn, P.W. et al. Construction of a yeast artificial chromosome spanning the spinal muscular atrophy disease gene region. Proc. natn. Acad. Sci. U.S.A. 90, 6801–6805 (1993).
Warburton, D. et al. Regional localization of 32 Notl-HindIII fragmnets from achromosome 13 library by a somatic cell hybrid panel and in situ hybridization. Genomics 16, 355–360 (1993).
Petrukhin, K.E. et al. A microsatellite genetic linkage map of human chromosome 13. Genomics 15, 76–85 (1993).
Weber, J.L. & Wong, C. Mutation of human short tandem repeats. Hum. molec. Genet. 2, 1123–1128 (1993).
Pirastu, M. et al. A founder effect for Wilson's disease in Sardinia defined by linkage disequilibrium mapping. Am. J. hum. Genet. (suppl.) 53, 844 (1993).
Thomas, G.R. et al. Allelic association and linkage studies in Wilson disease. Hum. molec. Genet. 2, 1401–1405 (1993).
Morral, N. et al. Microsatellite haplotypes for cystic fibrosis: mutations frameworks and evolutionary tracers. Hum. molec. Genet. 2, 1015–1022 (1993).
Fujimura, F.K. Cystic fibrosis gene analysis: recent diagnostic applications. Clin. Biochem. 24, 353–361 (1991).
Albertsen, H.M. et al. Construction and characterization of a yeast artificial chromosome library containing seven haploid human genome equivalents. Proc. natn. Acad. Sci. U.S.A. 87, 4256–4260 (1990).
Olsen, A.S. et al. Automated production of high density cosmid and YAC colony filters using a robotic workstation. Biotechniques 14, 116–123 (1993).
Evans, G.A., Lewis, K.A. & Rothenberg, B.E. High efficiency vectors for cosmid microcloning and genomic analysis. Gene 79, 9–20 (1989).
Chakravarti, A. et al. Nonuniform recombination within the human β-globin gene cluster. Am. J. hum. Genet. 36, 1239–1258 (1984).
Kerem, B. et al. Identification of the cystic fibrosis gene: genetic analysis. Science 245, 1073–1087 (1989).
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Petrukhin, K., Fischer, S., Pirastu, M. et al. Mapping, cloning and genetic characterization of the region containing the Wilson disease gene. Nat Genet 5, 338–343 (1993). https://doi.org/10.1038/ng1293-338
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DOI: https://doi.org/10.1038/ng1293-338
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